Signs Of Advanced Liver Disease Research Articles

Safety and Effectiveness Using 8 Weeks of Glecaprevir/Pibrentasvir in HCV-Infected Treatment-Naïve Patients with Compensated Cirrhosis: The CREST Study

IntroductionIn clinical trials with hepatitis C virus-infected treatment-naïve (TN) patients with compensated cirrhosis (CC), glecaprevir/pibrentasvir (G/P), a fixed-dose, once-daily, pangenotypic regimen, has demonstrated sustained virologic response at posttreatment Week 12 (SVR12) > 95%. We evaluated the real-world safety and effectiveness of 8-week G/P therapy in TN patients with CC, including certain subgroups of interest.MethodsThe CREST study is a real-world, noninterventional, multicenter study retrospectively assessing data from Canada, Germany, Israel, Italy, and Spain. The full analysis set (FAS) designated all patients in the study; the modified analysis set (MAS) excluded patients who discontinued G/P for nonvirologic failure or who had missing SVR12 data. The primary endpoint was SVR12; safety endpoints were also assessed.ResultsA total of 386 patients were included in the FAS, 375 patients completed the study, and 325 patients were included in the MAS; 51 patients had missing SVR12 data. Overall, in the MAS and FAS, SVR12 was achieved in 99.1% and 84.2% of patients, respectively. In subgroups of interest, the percentage of patients achieving SVR12 in the MAS (and FAS) was: genotype (GT)3: 97.5% (80.6%); FibroScan® ≥ 12.5 kPa: 98.9% (89.3%); platelet count < 100 × 109/l: 100% (88.2%); both platelets < 150 × 109/l and FibroScan® > 20 kPa: 100% (88.9%); aspartate aminotransferase-to-platelet ratio index > 1.09: 98.7% (83.1%); fibrosis-4 index > 3.25: 98.6% (84.0%); albumin < 3 g/dl: 100% (91.7%); people who use drugs: 97.7% (84.3%); psychiatric disorders: 96.6% (84.8%); and human immunodeficiency virus coinfection: 100% (95.0%). Overall, 26.9% (104/386) of patients experienced an adverse event, none of which were classed as serious.ConclusionIn this real-world cohort, 8 weeks of G/P therapy was well tolerated in TN patients with CC. SVR12 rates were similar to clinical trials, supporting 8-week treatment in TN patients with CC, including those with signs of advanced liver disease and GT3 infection.

Protocolo diagnóstico de la hepatopatía en el paciente oncológico

Liver disease suspicion in oncologic patients often is preceded by asymptomatic liver function tests disturbance, by imaging findings during cancer follow-up compatible with liver disease or, more rarely, by clinical symptoms or signs of advanced liver disease. Diagnosis has to be thorough, including both the commonest causes of liver disease as well as specific causes present in oncologic patient (consequence of chemotherapy, radiotherapy, co-administration of other drugs, liver tumor involvement, immunosuppression, etc.

Spontaneous Bacterial Peritonitis and Short-Term Prognosis in a Group of Decompensated Cirrhotic Patients in Yaounde: A Cross-Sectional Study

Introduction: Spontaneous bacterial peritonitis (SBP) is among the most common infections in cirrhotic patients. Data on SBP are rare in Cameroon. This prompted us to carry out this study on patients with decompensated cirrhosis of the liver in Yaounde University Hospital Centre (YUHC). Methods: We carried out a cross-sectional study from December 2015 to June 2016 in three units of YUHC. All patients with decompensated liver cirrhosis were included. Our sampling was consecutive. Diagnosis of cirrhosis was performed, based on clinical, biological and ultrasound criteria. A neutrophil count greater than 250 cell/mm3 in ascites fluid defined an SBP. Data on socio-demography, clinical presentation, and outcomes were collected. Results: We included 34 decompensated cirrhotic patients (15 males). Patients mean age was 57.5 ± 2 years (SBP positive: 48.7 ± 21.3 versus without SBP: 59.8 ± 19.5, p = 0.22). SBP diagnosis was made in 6 (17.7%) patients. Compared to patients with decompensated liver cirrhosis and without SBP, positive SBP patients had a higher pulse rate (p = 0.002) and respiratory rate (p = 0.02). The patients with SBP were more likely to present these other clinical features: pulse rate >100 (RR: 4.2, [95% CI: 0.7 - 27.7]; p = 0.02), presence of jaundice (RR: 3.4, [95% CI: 0.6 - 21.1]; p = 0.09), being from female gender (RR: 3.2, [95% CI: 0.5 - 19.9]; p = 0.11), advanced liver disease (Child C class) (RR: 2.4, [95% CI: 0.4 - 14.5], p = 0.66), low-plasma albumin (less than 20 g/L) (RR: 1.7, [95% CI: 0.8 - 3.9], p = 0.08), respiratory rate > 30 (RR: 1.6, [95% CI: 0.6 - 3.3], p = 0.05) and fever/hypothermia (RR: 1.5, [95% CI: 0.6 - 3.4]; p = 0.22). Evolution after a 72-hours antibiotherapy was stationary in four cases and unfavorable in two patients, resulting in death. Conclusion: SBP prevalence was 17.7%. SBP patients were younger, from female sex, tachycardia and polypnea, presenting with fever/hypothermia and signs of advanced liver disease than non-SBP patients. Improvement of our technical platform will be useful to determine the cause of cirrhosis and identify the different germs responsible for SBP.

Patients With Signs of Advanced Liver Disease and Clinically Significant Portal Hypertension Do Not Necessarily Have Cirrhosis

Patients with hepatic venous pressure gradients (HVPGs) of 10 mm Hg or greater and chronic liver disease often are assumed to have cirrhosis. We investigated the association between HVPGs and cirrhosis, using histologic findings as the reference standard. We also assessed the prevalence and characteristics of patients with HVPGs of 10 mm Hg or greater without cirrhosis. We performed a retrospective analysis of 157 consecutive patients, 89 with suspected cirrhosis and hepatic hemodynamic data collected from 2015 through 2017. Biopsy specimens collected had 10 or more portal tracts from each patient and were analyzed for features of cirrhosis. Biopsy specimens with histologic features of cirrhosis were excluded and the remaining biopsy specimens were re-reviewed by an expert pathologist. The fibrosis area was calculated digitally by image analysis. HVPG identified patients with cirrhosis with an area under the receiver operating characteristic curve of 0.879: 14 of 89 patients with HVPG of 10 mm Hg or greater (16%) had no histologic features of cirrhosis (METAVIR scores <4 and Ishak scores <6). The median HVPG was 11 mm Hg (range, 10-22 mm Hg). Based on METAVIR scores, 7 patients had fibrosis stage F3, 4 patients had fibrosis stage F2, and 3 patients had fibrosis stages F0 or F1. The mean area of fibrosis in livers was 16.2% ± 6.5%. All 14 patients had perisinusoidal fibrosis and 8 patients had hepatocyte ballooning. The most common diagnoses were nonalcoholic steatohepatitis (n= 5) and nodular regenerative hyperplasia (n= 4). An HVPG cut-off value of 12 mm Hg identified patients with cirrhosis with 92% specificity, misclassifying 5 patients with different etiologies of liver disease. In a retrospective analysis of 89 consecutive patients with chronic liver disease and an HVPG of 10 mm Hg or greater, 16% were not found to have cirrhosis upon biopsy analysis. Most of these patients had nonalcoholic steatohepatitis or nodular regenerative hyperplasia. Perisinusoidal fibrosis and hepatocyte ballooning might increase sinusoidal pressure. An HVPG cut-off value of 12 mm Hg or greater identified patients with cirrhosis with 92% specificity.

Liver-related Events in Human Immunodeficiency Virus-infected Persons With Occult Cirrhosis.

Human immunodeficiency virus (HIV)-infected patients are at increased risk of liver-related mortality. The effect of occult cirrhosis (OcC), defined as preclinical compensated cirrhosis without any clinical findings, on liver-related events is unknown. HIV-infected patients from 2 Canadian cohorts underwent transient elastography (TE) examination and were classified as (1) OcC (TE ≥13 kPa with no sign of cirrhosis, including absence of thrombocytopenia and signs of advanced liver disease on ultrasound or gastroscopy); (2) overt cirrhosis (OvC) (TE ≥13 kPa with signs of cirrhosis); or (3) noncirrhotic patients (TE <13 kPa). Incidence and risk factors of liver-related events were investigated through Kaplan-Meier and Cox regression analyses, respectively. We estimated monitoring rates according to screening guidelines for hepatocellular carcinoma (HCC) by OcC and OvC status. A total of 1092 HIV-infected patients (51% coinfected with hepatitis C virus) were included. Prevalence of OcC and OvC at baseline was 2.7% and 10.7%, respectively. During a median follow-up of 1.8 (interquartile range, 1.5-2.8) years, the incidence of liver-related events in noncirrhosis, OcC, and OvC was 3.4 (95% confidence interval [CI], 1.2-7.3), 34.0 (95% CI, 6.0-104.0), and 37.0 (95% CI, 17.0-69.1) per 1000 person-years, respectively. Baseline OcC (adjusted hazard ratio [aHR], 7.1 [95% CI, 1.3-38.0]) and OvC (aHR, 8.5 [95% CI, 2.8-26.0]) were independently associated with liver-related events. Monitoring rates for HCC were lower in patients with OcC (24%) compared to those with OvC (40%). HIV-infected patients with OcC have a high incidence of liver-related events. Greater surveillance and earlier recognition with appropriate screening strategies are necessary for improved outcomes.

Alcoholic liver disease.

Alcoholic liver disease (ALD) is the most prevalent type of chronic liver disease worldwide. ALD can progress from alcoholic fatty liver (AFL) to alcoholic steatohepatitis (ASH), which is characterized by hepatic inflammation. Chronic ASH can eventually lead to fibrosis and cirrhosis and in some cases hepatocellular cancer (HCC). In addition, severe ASH (with or without cirrhosis) can lead to alcoholic hepatitis, which is an acute clinical presentation of ALD that is associated with liver failure and high mortality. Most individuals consuming >40 g of alcohol per day develop AFL; however, only a subset of individuals will develop more advanced disease. Genetic, epigenetic and non-genetic factors might explain the considerable interindividual variation in ALD phenotype. The pathogenesis of ALD includes hepatic steatosis, oxidative stress, acetaldehyde-mediated toxicity and cytokine and chemokine-induced inflammation. Diagnosis of ALD involves assessing patients for alcohol use disorder and signs of advanced liver disease. The degree of AFL and liver fibrosis can be determined by ultrasonography, transient elastography, MRI, measurement of serum biomarkers and liver biopsy histology. Alcohol abstinence achieved by psychosomatic intervention is the best treatment for all stages of ALD. In the case of advanced disease such as cirrhosis or HCC, liver transplantation may be required. Thus, new therapies are urgently needed.

Liver histology in asymptomatic Hepatitis-C virus positive blood donors.

Objective:To assess the Histological alteration of liver in asymptomatic HCV PCR positive family blood donors.Methods:This is a prospective cross sectional study carried out at Blood Transfusion Services, Clinical & Molecular Laboratory and Pakistan Health Research Council, Jinnah Postgraduate Medical Centre, Karachi from January 2011 to December 2016. One hundred thirteen (113) Anti HCV and HCV RNA positive family blood donors with normal or slightly raised ALT during three consecutive bimonthly visits were included. After taking consent liver biopsy was done to see the histopathological changes in these study participants. The software program SPSS for windows (Ver.19) was utilized for all statistical analysis.Results:One hundred thirteen blood donors who were Anti HCV and HCV RNA positive were included. Ninety eight were male and 15 Female with a mean age of 32.3±6.94 years. Nineteen (16.8%) had significant inflammation of grade 2-3. Nine (8.0%) had significant fibrosis and steatosis was seen in 65 (57.5%) cases. Cirrhosis or advanced liver disease was not found in this series.Conclusion:HCV infected individual with normal ALT level having good physical health, without any sign of advanced liver disease on ultrasonography and routine laboratory investigation like AST, Gamma GT, Alkaline Phosphatase, serum albumin, A/G ratio, platelet count and PT, INR might be highly helpful to predict mild or progressive liver disease. Ultimately it reduces the need of liver biopsy, an invasive procedure having significant complications.

The Implications of Low Absolute CD4 Counts in Patients With Cirrhosis and Human Immunodeficiency Virus.

To the Editor—In their recent study, Baranoski et al [1] describe a high rate of liver disease progression in patients with human immunodeficiency virus (HIV)-hepatitis B virus coinfection and CD4 counts <200 cells/mm3. The authors suggest that more advanced immunosuppression in these patients may lead to accelerated liver fibrosis. Because only 50% of the HIV-infected patients were taking antiretroviral therapy at study entry and 78% had detectable HIV viremia, this is a reasonable explanation for the progression of liver disease in these patients with acquired immune deficiency syndrome. However, another possible explanation is that a low absolute CD4 count may be an independent marker of liver dysfunction, even in patients without HIV. For example, a 2007 study of 60 HIV-negative patients with cirrhosis found that 43% had CD4 counts <350 cells/mm3 and 7% had CD4 counts <200 cells/mm3 [2]. Yet although low absolute CD4 counts were common in this study, 95% of these patients had normal CD4 cell percentages. Likewise, several studies of patients with HIV and liver disease have found an association between advanced liver disease and discordant absolute CD4 counts and CD4 percentages [3, 4]. One hypothesis is that liver dysfunction and portal hypertension may lead to splenic sequestration of CD4+ T cells and a low absolute CD4 count, even as the CD4 percentage remains relatively intact [5, 6]. In these patients, the low absolute CD4 count may be a sign of advanced liver disease as opposed to advanced immunosuppression. The clinical and immunologic implications of a low absolute CD4 count but normal percentage in patients with HIV and cirrhosis remain unclear. In the study by Baranoski et al [1], it is possible that CD4 counts <200 cells/mm3 were more likely to occur in patients with hepatic fibrosis or splenomegaly, and therefore progression of liver disease was more likely among these patients as well. However, whether or not immunosuppression itself contributed to this progression merits further investigation. In this regard, it would be helpful to know the rates of low CD4 percentages in this study, and whether low percentages were also associated with worsening liver disease in these patients. A link between low CD4 percentage and liver disease progression would support the authors' arguments regarding immunosuppression promoting hepatic fibrosis, whereas lack of association might support consideration of other causes.

Occult cirrhosis diagnosed by transient elastography is a frequent and under-monitored clinical entity.

Diagnosis of preclinical compensated cirrhosis (occult cirrhosis, OC) is challenging due to lack of clinical findings. We evaluated prevalence and outcomes of OC by transient elastography (TE, Fibroscan(®)). Eight hundred and seventy-one patients with compensated chronic liver disease (CLD) and TE examination were divided into: (i) OC (TE ≥ 13 kPa and no sign of cirrhosis, including absence of thrombocytopenia and signs of advanced liver disease on ultrasound or gastroscopy); (ii) clinically evident cirrhosis (TE ≥ 13 kPa with signs of cirrhosis); (iii) non-cirrhotic CLD (TE < 13 kPa). Outcomes included hepatocellular carcinoma (HCC), esophageal varices and ascites. Late diagnosis of outcomes was defined as HCC stage ≥intermediate by BCLC or variceal bleeding. Occult cirrhosis represented 12% of the cohort and 37% of cirrhotic patients. Independent predictors of OC were age [odds ratio (OR) 1.15; 95% confidence interval (CI), 1.04-1.26], HIV co-infection (OR 3.53; 95% CI, 1.85-6.76) and APRI (OR 2.63; 95 CI, 1.87-3.71). During a median follow-up of 24 (interquartile range 20-37) months, OC received less surveillance than clinically evident cirrhosis, with fewer ultrasounds (2.7 ± 1.5 vs 3.6 ± 2; P < 0.001) and gastroscopies (2 ± 0.8 vs 2.6 ± 1.4; P < 0.001). Incidence of outcomes was 3.5/100 per person-years (PY) (95% CI, 0.1-6.9) in OC, 0 in non-cirrhotic CLD and 9.8/100 PY (95% CI, 0.3-19.3) in clinically evident cirrhosis (P < 0.001). Late diagnosis occurred more in OC than clinically evident cirrhosis (60 vs 15%, P = 0.01). Occult cirrhosis is a frequent and under-monitored clinical entity associated with short-term risk of outcomes. TE may help early diagnosis, prompt initiation of surveillance and specific therapy for an otherwise unrecognized condition.

Acute Fatal Presentation of Adult-onset Ornithine Transcarbamylase (OTC) Deficiency

Purpose: A 19-year-old soldier was admitted to ICU from an outside hospital with seizures. He was admitted there with altered mental status three days prior. An extensive work-up for infectious and toxic etiologies was negative at the time. He improved on empiric antibiotics and was discharged with a diagnosis of encephalopathy of unknown etiology. He was readmitted and transferred to our hospital with status epilepticus. History was negative for preceding viral prodrome, aspirin, recreational drug use, travel history, or insect bites. His developmental and family history was unremarkable, and he was only taking multivitamins. At admission, he was found to have a fever of 38.3 with tachycardia and normal blood pressure. Examination was significant for mild hepatomegaly with no signs of advanced liver disease. Neurological examination was non-focal with bilateral down-going planters and negative meningism. He was started on propofol, fosphenytoin, and levetiracetam with control of seizures. His comprehensive metabolic profile was significant for elevated creatinine at 1.88, elevated AST, ALT at 88, and 189 IU/ml with normal bilirubin, alkaline phosphatase, and synthetic functions. Ammonia level was significantly elevated at 1,248 mmol/L. Other work-up including acute hepatitis panel, iron studies, ANA, and serum ceruloplasmin were normal. CT head showed bilateral diffuse sulcal effacement. USG abdomen showed decreased parenchymal echogenicity. Lumbar puncture and a metabolic drug screen were normal. Patient was started on hemodialysis, along with IV infusions of ammonul, arginine and empiric levocarnitine, with improvement of NH3 down to 112 by the next day. Acylcarnitine profile, urine amino acids, urine orotic acid levels, and OTC comprehensive sequence and deletion duplication analysis were sent out. However, despite being off sedation, he displayed no signs of spontaneous neurological activity, and was declared brain dead after two formal assessments. His urine orotic acid level came back elevated at 225.9 mmol/mol, and his DNA analysis revealed R277W mutation at exon eight for OTC gene. OTC deficiency is the most common enzyme deficiency for urea cycle disorder. Being an X-linked pattern of inheritance, it most commonly affects males in infancy, with a wide range of clinical presentations. With more than 40 point mutations and nucleotide deletions described for the OTC gene, it has variable phenotypical presentations with variable severity and outcomes. Our case is a unique presentation at a later age, which is rare, and emphasizes the importance of considering as differential in any patient with altered mental status, irrespective of age, as prompt and early diagnosis has the potential to prevent lethal outcomes.

Use of Thrombopoietic Agents for the Thrombocytopenia of Liver Disease

Thrombocytopenia can be a sign of advanced liver disease. This complicates the management of these patients, as patients with advanced liver disease frequently need therapeutic interventions, which are associated with an increased risk of bleeding. Thrombocytopenia may even be more pronounced in patients with hepatitis C virus (HCV) infection. This can limit current and future treatments for HCV, which remains based on interferon therapy, and this therapy can worsen thrombocytopenia. Thus, the ability to increase platelets to higher and safer levels would be desirable, but no treatment has yet been proven effective and safe in this setting. The small molecule thrombopoietin mimetic, eltrombopag, has demonstrated a dose-response increase in platelet counts in a phase II study in HCV patients without significant side effects, allowing initiation and completion of a 12-week course of pegylated interferon plus ribavirin in 36%, 53%, and 65% of patients receiving 30 mg, 50 mg, or 75 mg eltrombopag daily, respectively, compared to only 6% in the placebo arm. A current phase III study is currently evaluating whether this treatment allows successful outcomes and sustained viral eradication.

Intraoperative pulmonary hypertension occurred in an asymptomatic patient with pre-existent liver cirrhotic and portal hypertension

Portopulmonary hypertension (PPH) is clinically defined as the development of pulmonary arterial hypertension complicated by portal hypertension, with or without advanced hepatic disease. Physical signs may be absent in mild to moderate PPH and only appear in a hyperdynamic circulatory state. Similar signs of advanced liver disease can be observed in severe PPH, with ascites and lower extremity edema. Pulmonary hypertension is usually diagnosed after anesthetic induction during liver transplantation (LT). We present intraoperative pulmonary hypertension in a 41-year-old male patient with hepatic cirrhosis. Since this patient had no preoperation laboratory data supporting the diagnosis of pulmonary hypertension and was asymptomatic for a number of years, it was necessary to send him to the intensive care unit after operation. Further study should be focused on the diagnosis and treatment of pulmonary arterial hypertension in order to reduce its mortality.

Modified Jejunoileal Bypass Surgery with Biliary Diversion for Morbid Obesity and Changes in Liver Histology During Follow-up

Background and aimsBariatric surgery is the most effective treatment for morbid obesity. The classic procedure, jejunoileal bypass, has many complications including rapid progress of liver disease. The senior author (I.F.) has developed a modification of jejunoileal bypass, which we believe overcomes many of the shortcomings of the classic procedure. MethodsConsecutive patients referring for bariatric surgery were included. A modified jejunoileal bypass in which the defunctionalized limb is eliminated by anastomosing its ends to the gall bladder and cecum was performed. Liver biopsies were taken during operation and at a mean of 16 months later. The patients were followed for 5 years. ResultsForty-three patients were enrolled. The mean value of weight and body mass index (BMI) fell from 128 kg and 46 kg/m2 before operation to 85 kg and 31 kg/m2 at 5 years, respectively (p < 0.001). There was no significant change in the degree of liver steatosis and necroinflammation. The mean liver fibrosis score increased from 0.1 to 0.9 (p = 0.015). No sign of advanced liver disease was observed during the 5-year follow-up. ConclusionThe modified jejunoileal bypass is very effective in inducing and maintaining weight loss for 5 years and does not lead to hepatic failure or rapid progression of liver disease.

Prevalence and risk factors of asymptomatic hepatitis C virus infection in Egyptian children

To identify the prevalence, risk factors and manifestations of asymptomatic hepatitis C virus (HCV) infection in Egyptian children. Children at the age of 1-9 years were screened for HCV antibodies and alanine aminotransferase (ALT) levels. Every child with elevated ALT and/or detectable HCV antibodies was tested for HCV RNA by RT-PCR and compared with two negative controls for risk factors and signs and symptoms of liver disease. We screened 1042 children, six of them had elevated ALT, negative HCV antibody and positive RNA, likely representing acute hepatitis C cases. Fifteen children were HCV seropositive, 5 of them were HCV RNA positive. Asymptomatic HCV infection was present in 2.02% (positive results for either HCV antibodies or HCV-RNA or both). Symptoms such as diarrhea, abdominal pain, history of fatigue and school absence because of illness and risk factors such as dental care were significantly more common among HCV positive cases than among controls. None of the HCV positive children was diagnosed as having signs of advanced liver disease upon clinical or ultrasonographic examination. Asymptomatic HCV infection is detectable in 2.02% Egyptian children.

Declines in Memory, Attention Can Be Signs of Advanced Liver Disease

Declines in Memory, Attention Can Be Signs of Advanced Liver Disease

Long‐term prognosis of nonalcoholic fatty liver disease: Is pharmacological therapy actually necessary?

Nonalcoholic fatty liver disease (NAFLD) comprises a wide spectrum of liver injury, ranging from steatosis and steatohepatitis to cirrhosis. Reasons for the different natural course in individuals with NAFLD are still unclear. The aim of this study was to describe the natural course of disease in individuals with NAFLD who did not receive pharmacological therapy. A total of 27 individuals with NAFLD (male/female ratio: 10/17, mean age 49.7 years) were prospectively enrolled. Management after diagnosis consisted of establishment of an appropriate diet and exercise (walking and jogging) program, treatment of associated metabolic conditions such as diabetes and dyslipidemia, and discontinuation of potentially hepatotoxic drugs if the patient was taking these. Liver tests were performed at diagnosis and at 3-month intervals during the follow-up period. Mean follow-up period was 43.3 months (range 36-49 months). From baseline to the end of the follow-up period, although there was no significant difference observed in terms of the mean body mass index, serum aminotransferase levels significantly improved (48.8+/-29.9 U/L to 31.6+/-16.0 U/L for aspartate aminotransferase [AST] and 66.3+/-38.3 U/L to 39.6+/-22.9 U/L for alanine aminotransferase [ALT]; P<0.05). No significant differences in platelet counts, serum albumin level or prothrombin time were observed (P>0.05). No patient developed signs of advanced liver disease during the follow-up period. A treatment strategy comprising diet, exercise and management of associated metabolic conditions is associated with improvement in aminotransferases among patients with NAFLD. Further investigation is needed to examine the long-term efficacy of this approach on liver histology and clinical outcomes.

Early referral is essential for successful pediatric small bowel transplantation: The Canadian experience

Purpose: The mortality rate for pediatric patients on the waiting list for transplantation has a major impact on the overall effectiveness of pediatric small bowel transplantation. This review was undertaken to determine the fate of Canadian children assessed for small bowel transplant and the outcome of those who undergo transplant in the tacrolimus era. Methods: The authors reviewed retrospectively all of the pediatric small bowel patients listed since 1988 through the Canadian Organ Replacement Register and all the children referred to our program in its first year. All children who received a small bowel transplant between January 1993 and December 1999 also were reviewed. Results: The mortality rate for pediatric patients on the small bowel transplant list was 53% after an average of 105 days on the list compared with 212 days for those who underwent transplant. Patients who died while on the list were younger and had signs of advanced liver disease at the time of listing. Thirteen Canadian children have received a small bowel transplant with an overall 1-year patient and graft survival rate of 61% and 53%, respectively. Survivors are all independent from total parenteral nutrition. Conclusion: Many Canadian children miss their opportunity for a successful small bowel transplant because of late referrals and a shortage of donor organs. J Pediatr Surg 36:681-684. Copyright © 2001 by W.B. Saunders Company.

Morbidity of chronic hepatitis C as seen in a tertiary care medical center.

We studied the morbidity of chronic hepatitis C in patients referred to a tertiary care medical facility. The medical records of 500 consecutive cases of chronic hepatitis C were examined for the following: (1) source and time of exposure, (2) signs and symptoms of liver disease, (3) degree of alcohol intake, (4) liver biopsy findings, (5) extrahepatic disease manifestations, and (6) coexisting illnesses that could have an impact on morbidity. Morbidity and histologic findings were evaluated in relation to the duration of hepatitis C. The onset of infection could be determined in 376 patients (75%). A close relationship between the length of infection and disease features was not observed. Fatigue was common at all stages of infection. Whereas cirrhosis occurred more frequently in patients with disease of long duration, 15-24% of patients had signs of advanced liver disease (ascites, encephalopathy, thrombocytopenia) within six years of exposure. Overt extrahepatic manifestations of chronic hepatitis C occurred infrequently, and depression was reported in 24% of untreated patients. In conclusion, in patients referred to a tertiary care setting, chronic hepatitis C is often associated with significant morbidity.